Hemorrhage management system

ABSTRACT

An embodiment includes a wound dressing comprising: a shape memory polymer (SMP) foam, including open cells, having first and second states; and a hydrogel (HG) included within the cells; wherein (a) in a first position a composite, including the SMP foam and the HG, is configured to be located proximate a hemorrhagic tissue with the SMP foam in the first state; (b) in a second position the composite is configured to be expanded to the second state against the hemorrhagic tissue when the SMP foam is plasticized at 37° C. depressing a glass transition temperature (T g ) of the SMP foam to below 25° C. Other embodiments are described herein.

This application is a continuation of U.S. patent application Ser. No.14/661,215, filed Mar. 18, 2015, and entitled “Hemorrhage ManagementSystem”. The content of the above application is hereby incorporated byreference.

STATEMENT AS TO RIGHTS TO APPLICATIONS MADE UNDER FEDERALLY SPONSOREDRESEARCH AND DEVELOPMENT

The United States Government has rights in this application pursuant toContract No. DE-AC52-07NA27344 between the United States Department ofEnergy and Lawrence Livermore National Security, LLC for the operationof Lawrence Livermore National Laboratory.

BACKGROUND Field of Endeavor

The present application relates to hemorrhages and more particularly toa hemorrhage management system.

State of Technology

This section provides background information related to the presentdisclosure which is not necessarily prior art.

Approximately 50% of combat and 80% of civilian trauma fatalities aredue to uncontrolled hemorrhage. Exsanguination is a leading cause ofpre-hospital death. An estimated 80% of trauma wounds are not amenableto compression or tourniquets. To treat such hemorrhage conditions,there are at least three conventional hemorrhage control systems:compression (applying pressure directly to a wound), hemostatic gauze(incorporating procoagulants to minimize time to hemostasis), andexpandable foams (used to expand within a wound and direct pressure onthe wound).

SUMMARY

Features and advantages of the disclosed apparatus, systems, and methodswill become apparent from the following description. Applicant isproviding this description, which includes drawings and examples ofspecific embodiments, to give a broad representation of the apparatus,systems, and methods. Various changes and modifications within thespirit and scope of the application will become apparent to thoseskilled in the art from this description and by practice of theapparatus, systems, and methods. The scope of the apparatus, systems,and methods is not intended to be limited to the particular formsdisclosed and the application covers all modifications, equivalents, andalternatives falling within the spirit and scope of the apparatus,systems, and methods as defined by the claims.

The scope of the disclosed apparatus, systems, and methods comprises allof the features of novelty of the hemorrhage management system as shownand described.

The apparatus, systems, and methods are susceptible to modifications andalternative forms. Specific embodiments are shown by way of example. Itis to be understood that the apparatus, systems, and methods are notlimited to the particular forms disclosed. The apparatus, systems, andmethods cover all modifications, equivalents, and alternatives fallingwithin the spirit and scope of the application as defined by the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated into and constitute apart of the specification, illustrate specific embodiments of theapparatus, systems, and methods and, together with the generaldescription given above, and the detailed description of the specificembodiments, serve to explain the principles of the apparatus, systems,and methods. Features and advantages of embodiments of the presentinvention will become apparent from the appended claims, the followingdetailed description of one or more example embodiments, and thecorresponding figures. Where considered appropriate, reference labelshave been repeated among the figures to indicate corresponding oranalogous elements.

FIG. 1 depicts expansion force vs. temperature for various embodimentsof the invention.

FIGS. 2(a) and 2(b) depict tunability of embodiments of the inventionbased on hydrogel composition.

FIG. 3 depicting Raman spectroscopy results indicating that the SMPfoam/HG complex shows spectral changes correlating to successful doping.

FIGS. 4(a) and 4(b) illustrate overall the iodine doped composites havea minimal effect on the physical properties of embodiments.

FIGS. 5(a), (b), and (c) illustrate pre-crimp (permanent shape) andpost-crimp (secondary shape) embodiments of the invention.

FIGS. 6(a) and (b) are images of embodiments of the invention.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

Referring to the drawings, to the following detailed description, and toincorporated materials, detailed information about the apparatus,systems, and methods is provided including the description of specificembodiments. The detailed description serves to explain the principlesof the apparatus, systems, and methods. The apparatus, systems, andmethods are susceptible to modifications and alternative forms. Theapplication is not limited to the particular forms disclosed. Theapplication covers all modifications, equivalents, and alternativesfalling within the spirit and scope of the apparatus, systems, andmethods as defined by the claims.

Reference will now be made to the drawings wherein like structures maybe provided with like suffix reference designations. In order to showthe structures of various embodiments more clearly, the drawingsincluded herein are diagrammatic representations of structures. Thus,the actual appearance of the structures, for example in an image, mayappear different while still incorporating the claimed structures of theillustrated embodiments. Moreover, the drawings may only show thestructures useful to understand the illustrated embodiments. Additionalstructures known in the art may not have been included to maintain theclarity of the drawings. “An embodiment”, “various embodiments” and thelike indicate embodiment(s) so described may include particularfeatures, structures, or characteristics, but not every embodimentnecessarily includes the particular features, structures, orcharacteristics. Some embodiments may have some, all, or none of thefeatures described for other embodiments. “First”, “second”, “third” andthe like describe a common object and indicate different instances oflike objects are being referred to. Such adjectives do not imply objectsso described must be in a given sequence, either temporally, spatially,in ranking, or in any other manner. “Connected” may indicate elementsare in direct physical or electrical contact with each other and“coupled” may indicate elements co-operate or interact with each other,but they may or may not be in direct physical or electrical contact.

Compression is lacking in that it does not reduce risk of infection, isonly applicable to specific wounds, and has an extended time to clotformation. Hemostatic gauze is not ideal because it can cause thermaltissue damage, does not reduce the risk of infection, is vulnerable tohigh rebleed rates, and has the potential to cause systemic exposure ofthe procoagulant. Conventional expandable foams are problematic becausethey are difficult to remove from the wound, do not reduce the risk ofinfection, and have limited efficacy data.

In contrast, an embodiment satisfies various characteristics forsuperior hemorrhage management system such as: (1) stops severearterial/venous bleeding in less than 2 minutes, (2) swells to absorbwound exudate, (3) is flexible enough to conform to complex woundgeometries, and (4) protects against bacterial infection. One suchembodiment includes a composite comprising a shape memory polymer (SMP)foam and a Poly(ethylene gylcol) Diacrylate (PEG-DA) N-vinylpyrrolidone(NVP) hydrogel (HG).

SMPs are polymeric smart materials that have the ability to return froma deformed state (temporary shape) to their original (permanent) shapeinduced by an external stimulus (trigger), such as temperature change.SMPs can retain two or more shapes, and the transition between those isinduced by temperature. In addition to temperature change, the shapechange of SMPs can also be triggered by an electric or magnetic field,light, or solvent plasticization. As well as polymers in general, SMPsalso cover a wide property-range from stable to biodegradable, from softto hard, and from elastic to rigid, depending on the structural unitsthat constitute the SMP. SMPs include thermoplastic and thermoset(covalently cross-linked) polymeric materials.

Inclusion of a SMP in the complex is advantageous. A SMP includingHexamethylene diisocyanate (HDI), triethanolamine (TEA), andhydroxypropyl ethylenediamine (HPED) exhibited biocompatibility in aporcine side wall aneurysm, up to 100× volume expansion, is conformableto unique wound geometry, and has demonstrated occlusion in porcine hindlimbs in less than 90 seconds. In an embodiment, when plasticized in 37°C. water, the glass transition temperature (T_(g)) is depressed to ˜12°C. This allows for actuation when exposed to fluids at body temperature.In an embodiment the SMP foam was cleaned to remove unreacted reagentsand reticulated to make an open pore structure. Pore sizes are tunableto between 200-1500 μm. In an embodiment the SMP foam is hydrophilic.Various embodiments have tuned hydrophilicity for the SMP so the devicesactuate at different rates.

An HG is a network of polymer chains that are hydrophilic, sometimesfound as a colloidal gel in which water is the dispersion medium. HGsare highly absorbent (they can contain over 90% water) natural orsynthetic polymeric networks. HGs also possess a degree of flexibilityvery similar to natural tissue, due to their significant water content.

Inclusion of a PEG-DA-NVP HG in the complex is advantageous. Such an HGswells 20-100× its original mass in water, will complex with elementaliodine to form povidone-iodine (PVP-I₂) (Betadine) to provideantibacterial properties, and can be formulated to be biodegradable andbiocompatible. Embodiments use various molecular weights of PEG, somewith a high ratio of polyvinylpyrrolidone (PVP), which are thermallycured with excess hydrogel removed and then dried.

In an embodiment hydrophilic polyurethane SMP foams were cut intocylinders 8 mm in diameter and 20 mm in length. Then a PEG-DA hydrogelsolution was complexed with iodine and cast into a PTFE mold containingthe foam cylinders to create the SMP foam-HG composite. “Complexed” inthis instance means the HG solution is mixed with iodine, and due tocharges on some of the molecules in the HG, the iodine molecules areattracted by the HG branches essentially bonding the iodine to the PVPin the hydrogel. While the bond may not amount to a true covalent bond,there is a strong attraction between the two compounds that allows for acontrolled release of iodine from the composite.

An embodiment of the complex of SMP and HG still retains the SMcharacteristics of the SMP alone (where Shape Recovery=(H″/H)(100) andH″ is length after expansion and H is length before crimping). Forexample, a control SMP foam had a Pre Crimp Diameter (mm)=5.57, CrimpedDiameter (mm)=0.74, Diameter after 15 min in 37° C. H₂O=5.39, and %Shape Recovery=96.8%. Similarly, a composite/complex of SMP foam and HGin an embodiment has Pre Crimp Diameter (mm)=5.89, Crimped Diameter(mm)=1.33, Diameter after 15 min in 37° C. H₂O=5.16, and % ShapeRecovery=87.6%.

Also, an embodiment of the complex of SMP and HG has a strong ability toconform to and fill a wound area (where Expansion Ratio=(H″/H′) and H″is length after expansion and H′ is length after crimping). A control SMfoam has an expansion ratio of 7.2 while a composite/complex of SMP foamand HG in an embodiment has an expansion ratio of 4.2.

Also, an embodiment of the complex of SMP and HG has strong swellability(where Q=(mass of saturated device)/(mass of dry device)), as evidencedby the following: SMP foam Q=1.1, SMP Foam-HG composite Q=23.6, andHG=29.1. Thus, in an embodiment addition of an HG to the SMP foamresults in a 20× increase in fluid uptake in regards to a SMP foamalone.

Further, an embodiment of the SMP foam/HG complex provides adequateforce applied to the wound boundary during expansion (see FIG. 1). As aresult, the increase in constrained recovery force reduces thelikelihood of device dislocation with a force that is not so excessiveas to cause tissue damage. Dynamic Mechanical Analysis (DMA) was usedfor data collection for FIG. 1, which shows an increase in recoveryforce for embodiments including iodine and without iodine as compared toa control SMP foam.

FIGS. 2(a) and 2(b) depict tunability of embodiments of the inventionbased on hydrogel composition, where thermograms are dominated by HGproperties and Tg of SMP foams is ˜67° C. when dry. These figuresdemonstrate the actuation temperature and Tg of the composite can betuned via altering the molecular weight and concentration of the PEG inthe HG. These figures show the thermomechanical properties of the HGremain intact after complexing with iodine and being incorporated intothe composite.

Further, in a bacterial adhesion study Staphylococcus aureus bacteriawere incubated with HGs using a Cell Titer96® assay to quantify adherentbacteria. Iodine-doped HGs demonstrate antibacterial properties asopposed to HGs not including iodine. In an embodiment, iodine doping ofthe HG may be performed using heat and aqueous mixing of the HGmaterials with a subsequent brown coloration of the device. Using Ramanspectroscopy a quantifiable method correlated with the presence of anIodine complex wherein I₃ forms when bound to PVP (see FIG. 3) such thatthe SMP foam/HG complex shows spectral changes correlating to successfuldoping. In an embodiment the addition of iodine was shown to have noadverse effect on the physical properties of doped composites, whereinno substantive change was observed with respect to swelling ratio (wheredoped and undoped composites both exhibited about a 20× swellingincrease over control SMP foam), percent recovery (where doped andundoped composites both exhibited a recovery of about 93%), andexpansion rate (where doped and undoped composites both exhibitedcomplete expansion within 2 minutes) (see also FIGS. 4(a) and (b)).Embodiments with Iodine provide self-sterilizing devices without changesin composite properties.

Thus, various embodiments provide a hemostatic wound dressing which: (a)retains its shape memory characteristics even after the introduction ofhydrogel and iodine, (b) is inherently antibacterial to preventinfection if used in the field, (c) shows more than 20× increase influid uptake to absorb wound exudate and swells to 23× the original massto allow exudate absorption and minimize potential bacteriacolonization, (d) demonstrates more than 10× increase in recoverystrength to prevent device dislocation, (e) easily deforms/conforms tofill complex wound geometry, (f) experiences more than 400% plasticstrain recovery upon contact with blood to provide optimal volumefilling, (g) is biocompatible.

An embodiment includes a kit having multiple SMP foam/HG compositedevices such that more than one device may be employed to substantiallyfill a large wound or void or void having a particularly irregularshape. The kit may include gauze, wraps, and/or bandages to providesupplemental help in holding SMP foam/HG composite devices in place.

An embodiment employs the SMP foam/HG composite as a wound dressing. Thedevice rapidly stops excessive internal and external bleeding, whilealso preventing bacterial infection by means of an antibacterial HGcoating. The HG coating also enhances the SMP foam's ability to absorbfluid to aid in the wound healing process. The mechanical and thermalproperties of the foam are tailored to meet the specific needs ofspecific wound geometries and locations (e.g., increased recovery forceis required for higher flow, arterial bleeding conditions), and variousantibacterial and thrombogenic compounds (e.g., kaolin, chitosan,silicate nanoparticles, bioactive glass particles, diatomaceous earth,and hydrogen peroxide) are easily combined with the HG coating tooptimize the wound healing properties of the hemostatic foam device. Thefoams are heated above their T_(g), held in the desired geometry forpackaging, and cooled below their T_(g) to retain their programmed shapeuntil plasticized. The foams are either injected into or placed over thewound area, plasticized, and use their SM behavior to fill the entire,unique geometry of the wound. In an embodiment, the device applicatorconsists of a waterproof, sealed syringe that allows the devices to beinjected directly into the wound volume. After placement, hemostasisoccurs in less than five minutes in some embodiments, while theantibacterial properties of the foam act immediately upon contact withthe wound surface.

In an embodiment the syringe or applicator is sealed to prevent anypremature device actuation. The applicator may include numerouscomposite devices (e.g., SMP foam/HG beads). In embodiment theapplicator also deposits an additional antibacterial agent (e.g.,hydrogen peroxide) when the device(s) are released into the wound. Thisapplicator may include a double barrel syringe where the compositedevices do not mix with the additional antibacterial agent until boththe composite devices and the additional antibacterial agent have exitedthe applicator.

Embodiments can be used to replace or augment conventional gauze totreat hemorrhage and absorb fluid in surgical applications, as well asan alternative to current hemostatic sponge products used throughout themilitary and civilian emergency response units to treat traumaticinjuries and control extreme hemorrhage. Aside from military andfirst-responder use, these SMP foam/HG composites may be used to helptreat diabetic ulcers and encourage reendothelialization and properhealing of open sores. The SMP foam may act as a tissue scaffold andencourage connective tissue infiltration and subsequent endothelial cellgrowth and proliferation within the sore.

A significant aspect of various embodiments is their ability to be usedin many traumatic injuries where hemorrhage is involved. Suchembodiments are not limited by their ability to only prevent bleeding incertain applications or wound types. This results in a universal productto treat any form or most forms of uncontrolled bleeding. This allowsfirst-responders to stabilize traumatic injury patients before arrivingat the hospital, and provides an easy-to-use, effective means forsoldiers to stop the excessive bleeding of a fellow soldier orthemselves. With uncontrolled hemorrhage being the cause of more than50% of deaths in the battlefield and civilian trauma centers, these SMPfoam/HG devices will save lives of individuals who would otherwise dieas a result of exsanguination.

This stands in contrast to current hemostatic sponges that are used forinternal or external bleeding, often without any antimicrobialproperties.

In contrast, conventional hemostatic sponge products used to controlbleeding cannot be implanted. Such products have to be removed from thewound bed after a few hours. Alternatively, injectable foams (e.g., soapfoam and the like) that are used to control internal bleeding duringsurgery are not used for exposed, external wounds because of thepotential for bacterial infection and their limited mechanicalintegrity/properties. However, an embodiment of the SMP foam/HGcomposite has the mechanical strength (e.g., from the SMP foam and/orHG) and antibacterial properties (e.g., from iodine infused HG) to allowexternal use and internal use due to the biocompatibility of the SMPfoam and HG and the antibacterial component of various embodiments.

Also, conventional hemostatic sponge products must be frequently changedas a result of potential bacterial and fungal infections. But SMPfoam/HG embodiments described herein can also be used to control bothinternal and external bleeding. In addition, the ability to conform toany size and shape of a wound to provide complete coverage is unique toembodiments described herein. This provides more robust wound coveragethat can withstand arterial blood flow pressures, allows one device tobe used to treat a vast array of injury sites and size of wound, doesnot require device placement in a specific location inside the wound,and ensures that healthy tissue is isolated from damaged tissue.

In various embodiments the HG/SMP foam are combined in various ways. Forexample, in one embodiment they are combined simply by submerging theSMP foam into an HG solution, withdrawing the SMP foam from thesolution, and then heating the SMP/HG combination to crosslink thehydrogel. In another embodiment, the SMP foam is placed in a mold (e.g.,a hole drilled into a block of polymer with the same diameter as thefoam). A HG solution is then poured into the mold. The combination isthen heated to crosslink the hydrogel.

In an embodiment, the HG is found throughout the SMP foam or variousportions of the SMP foam. The HG deposits in small portions on struts ofthe SMP foam and/or forms a thin membrane on the struts (see FIG. 6(b),wherein the scale in the background is in cm). The HG may also fill theentire volume (or almost the entire volume) of the foam (see FIG. 6(a),wherein the scale in the background is in cm). In an embodiment smallpieces of SMP/HG complex (e.g., beads) are injected into a woundprovided those pieces are large enough to avoid entering into and beingcommunicated within a patient's vasculature. Such an embodiment mayallow for a higher HG concentration to increase the moisture absorptioncapacity of the foam. In another embodiment, the SMP/HG combinationdevice is attached to a bandage so the device is placed in the wound andthen pressed against the wound based on the bandage pressing against thepatient.

In an embodiment a kit may include embodiments such as those of FIGS.6(a) and 6(b). In such a case the preferred embodiment between theembodiments of FIGS. 6(a) and 6(b) depends on the therapeutic goal. Forexample, the embodiment of FIG. 6(b) may expand more rapidly than thatof FIG. 6(a) but the HG may more easily decouple from the foam. The HGof FIG. 6(a) may be more stable within the foam and be more resistant todecoupling from the foam than that of FIG. 6(b). A kit may provideinstructions to a user to initially utilize the embodiment of FIG. 6(b)and then to follow such treatment by utilizing the embodiment of FIG.6(a).

In an embodiment, the SMP foam is covered with iodine-doped HG solutionand then heated to crosslink the HG about the SMP foam. Uponcrosslinking, the HG adheres to the foam struts.

A method includes the following: (1) the SMP foam/HG device is heatedabove its T_(g) and held in the desired geometry for packaging; (2) thedevice is cooled below its T_(g) to program the packaged shape into thedevice; (3) the device is sterilized under EtO sterilization andpackaged and stored at temperatures less than 30 degrees Celsius; (4) toapply the hemostatic sponge, it is removed from the package and insertedanywhere within the wound area; (5) the wound area is covered with acloth, bandage, or hydrogel graft and the foam plasticizes at bodytemperature to expand and fill the entire geometry of the wound; and (6)pressure is applied until hemostasis is observed.

An embodiment includes a SMP foam/HG composite comprising isocyanate,hexamethylene diisocyanate (HDI), trimethyl hexamethylene diisocyanate(TMHDI), N,N,N′,N′-tetrakis(hydroxypropyl)ethylenediamine (HPED),triethanolamine (TEA), isophorone diisocyanate (IPDI), polyethyleneglycol (PEG) diacrylate (DA), polyethylene diacryamide, PEGdiacrylamide-N-vinylpyrrolidone (NVP), hyaluronic acid,poly(2-hydroxyethyl methacrylate) (polyHEMA), polyvinyl alcohol (PVA),polyvinyl acetate (PVAc), iodine, deoionized water, 3-sulfopropylacrylate potassium salt, 2-hydroxyethyl acrylate, polypropylene glycoldiacrylate, ethylene glycol dimethacrylate, tetra(ethylene glycol)diacrylate, thrombin, azobisisobutyronitrile, benzoyl peroxide,2,2-dimethoxy-2-phenylacetophenone, butanediol, propanediol,pentanediol, diethyleneglycol, dipropylene glycol, diethanolamine,dibutalene glycol, hexamethylenediamine, hydrogenated4,4′-Methylenebis(cyclohexyl isocyanate), PEG diacrylamide—NVP and othercompositions.

An embodiment includes a SMP foam/HG composite comprising HDI, HPED,TEA, PEG-DA, NVP, iodine, and deionized water.

An embodiment includes a SMP foam/HG composite comprising HDI, HPED,TEA, PEG-DA, NVP, hyaluronic acid, iodine, and deionized water.

An embodiment includes a SMP foam/HG composite comprising TMHDI, HPED,TEA, PEG-DA, NVP, hyaluronic acid, iodine, and deionized water.

An embodiment includes a SMP foam/HG composite comprising TMHDI, HPED,TEA, PEG-DA, NVP, iodine, and deionized water.

An embodiment includes a SMP foam/HG composite comprising IPDI, HPED,TEA, PEG-DA, NVP, hyaluronic acid, iodine, and deionized water.

An embodiment includes a SMP foam/HG composite comprising IPDI, HPED,TEA, PEG-DA, NVP, iodine, and deionized water.

An embodiment includes a SMP foam/HG composite comprising HDI, HPED,TEA, PEG-DA, polyHEMA, NVP, iodine, and deionized water.

An embodiment includes a SMP foam/HG composite comprising HDI, HPED,TEA, PEG-DA, NVP, thrombin, iodine, and deionized water.

An embodiment includes a SMP foam/HG composite comprising HDI, HPED,TEA, PEG-DA, NVP, thrombin, hyaluronic acid, iodine, and deionizedwater.

In an embodiment the SMP foam includes a crosslinked thermosetpolyurethane polymer comprising a covalently bonded network structureand a reaction product of an aliphatic diisocyanate monomer reacted withat least one symmetric hydroxyl containing monomer; wherein said polymerhas shape memory behavior and is formed into a permanent primary shape,re-formed into a stable secondary shape, and is configured to becontrollably actuated to recover said permanent primary shape; whereinthe diisocyanate monomer and the at least one symmetric hydroxylcontaining monomer are formulated to a 1:1 ratio of isocyanate tohydroxyl functional groups; wherein the at least one symmetric hydroxylcontaining monomer includes at least one of N,N,N′,N′-tetrakis(2-hydroxypropyl) ethylenediamine (HPED) and triethanol amine (TEA);wherein the polymer has a Young's modulus in a range of 1 to 100 MPa ata temperature above a glass transition temperature of the polymer.

In an embodiment an HG is grafted to a SMP foam surface as well.

In an embodiment wherein the diisocyanate monomer includes HDI, and theat least one symmetric hydroxyl containing monomer includes HPED andTEA. In an embodiment the diisocyanate monomer is symmetric instructure. In an embodiment the HDI composes between 53-61 weight % ofthe polymer, the HPED composes between 10-47 weight % of the polymer,and the TEA composes less than 29 weight % of the polymer.

FIGS. 5(a), (b), and (c) illustrate pre-crimp (permanent shape) andpost-crimp embodiments of the invention. As shown therein, in FIG. 5athe post-crimp image is generally planar whereas FIGS. 5(b) and (c) showpost-crimp images that are cylindrical with FIG. 5(b) being straw-likeand FIG. 5(c) being pellet-like. All three post-crimp forms result inthe same permanent cylindrical shape. However in other embodiments apermanent and/or post-crimp shape may be rectangular, ovular, spherical,and the like.

The following examples pertain to further embodiments. Example 1includes a wound dressing comprising: a shape memory polymer (SMP) foam,including open cells, having first and second states; and a hydrogel(HG) included within the cells; wherein (a) in a first position acomposite, including the SMP foam and the HG, is configured to belocated proximate a wound with the SMP foam in the first state; (b) in asecond position the composite is configured to expand to the secondstate within the wound when the SMP foam is plasticized at 37° C.depressing a glass transition temperature (T_(g)) of the SMP foam tobelow 25° C.

For example, “when the SMP foam is plasticized at 37° C.” includesplasticization across a spectrum of temperatures. For example,plasticization may occur over a range of temperatures such as, forexample, from 33° C. to 40° C. wherein 37° C. is included therein butwhere plasticization also occurs at 35° C. and 39° C. Further,“depressing a glass transition temperature (T_(g)) of the SMP foam tobelow 25° C.” includes depressing the T_(g) to, for example, 24, 23, 22,21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2,1, 0° C. and the like. A HG “included within the cells” includes, forexample, HG completely filling a cell, partially filling a cell, orcoating a strut of a cell. Further, “proximate a wound” includesexternal and internal applications applying to, for example, lacerationsof the skin as well as lacerations that are internal to a patient (e.g.,a wound in the liver intentionally caused by a surgeon's scalpel) andcaused by surgery and/or trauma.

In example 2 the subject matter of the Example 1 can optionally includewherein the SMP foam includes polyurethane and the HG includesPoly(ethylene gylcol) Diacrylate (PEG-DA) N-vinylpyrrolidone (NVP)(PEG-DA-NVP HG).

In example 3 the subject matter of the Examples 1-2 can optionallyinclude wherein the SMP foam includes two or more members selected fromthe group comprising Hexamethylene diisocyanate (HDI), triethanolamine(TEA), and hydroxypropyl ethylenediamine (HPED).

For example, an embodiment includes TEA and HDI but no HPED. Anotherembodiment may include HPED and HDI but not TEA. Of course otherembodiments are not so constrained and may include all three of HPED,HDI, and TEA, only one of those, or none of those.

In example 4 the subject matter of the Examples 1-3 can optionallyinclude wherein the SMP foam actuates at body temperature.

As used herein, “body temperature” is meant to convey a normal bodytemperature range. Normal body temperature varies by person, age,activity, and time of day. The average normal body temperature isgenerally accepted as 98.6° F. (37° C.) however the “normal” bodytemperature can have a wide range, from 97° F. (36.1° C.) to 99° F.(37.2° C.). A temperature over 100.4° F. (38° C.) may indicate a feverbut would still be a condition within the range of example 4.

In example 5 the subject matter of the Examples 1-4 can optionallyinclude wherein the HG is doped with an antimicrobial agent.

Doping in this context conveys the agent is added to the HG with nospecific chemical bond necessarily implied.

In example 6 the subject matter of the Examples 1-5 can optionallyinclude wherein the antimicrobial agent includes iodine.

As used in this context “iodine” includes derivatives therefrom.

In example 7 the subject matter of the Examples 1-6 can optionallyinclude wherein the iodine is bound to polyvinylpyrrolidone (PVP)included in the HG.

In example 8 the subject matter of the Examples 1-7 can optionallyinclude a member selected from the group comprising: kaolin, chitosan,silicate nanoparticles, bioactive glass particles, diatomaceous earth,and hydrogen peroxide.

In example 9 the subject matter of the Examples 1-8 can optionallyinclude a syringe that includes the composite and a plurality ofadditional composites, each of the additional composites including anadditional SMP foam with additional cells that include additional HGs.

For example, an embodiment may include SMP foam/HG beads to be deployedfrom a syringe.

In example 10 the subject matter of the Examples 1-9 can optionallyinclude wherein the SMP foam is configured to conform to contours of thewound, when in the second position and the second state, based on theSMP foam having % Shape Recovery greater than 100, expansion ratiogreater than 4, and swellability (Q) greater than 20 where Q=(mass ofsaturated device)/(mass of dry device).

Embodiments cover a variety of scenarios including, for example, % ShapeRecovery=80, 85, 90, 95, 100, 105, 110, 115, 120, 125 and the like,Expansion Ratio=1.00, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 9.00,10.00 and the like, and Q=18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30, 31, 32 and the like.

In example 11 the subject matter of the Examples 1-10 can optionallyinclude wherein the cells are reticulated.

For example, the reticulation may be partial or full.

In example 12 the subject matter of the Examples 1-11 can optionallyinclude wherein (a) the SMP foam and HG are both biodegradable, and (b)the composite is a medical implant configured for permanent implantationwithin a patient until the composite biodegrades within the patient.

In another version of example 12 the subject matter of the Examples 1-11can optionally include wherein the SMP foam and HG are both biostable,and the composite is a medical implant configured for permanentimplantation within a patient.

As used herein, “biostable” means the biostable element does not degradewithin the body.

In example 13 the subject matter of the Examples 1-12 can optionallyinclude wherein the SMP foam is crosslinked and includes struts, whichform the cells, and the HG is crosslinked around struts.

For example, in an embodiment the HG is not crosslinked until it isalready impregnated within the foam. In the same embodiment the foam iscrosslinked before the HG is impregnated within the foam. As a result,“HG is crosslinked around struts” provides for mechanical stabilityconsidering the HG is actually formed around the struts and thencrosslinked in that same position. In such an embodiment, a completelypolymerized, reticulated, cleaned, and dried foam is provided and thenexposed to a HG solution. The foam/HG solution is then heated tocompletely crosslink the HG while the HG is on the foam.

In example 14 the subject matter of the Examples 1-13 can optionallyinclude wherein the SMP foam is a thermoset polymer that includespolyurethane.

In example 15 the subject matter of the Examples 1-14 can optionallyinclude wherein in the first state the composite is generallycylindrical.

In example 16 the subject matter of the Examples 1-15 can optionallyinclude wherein in the first state the composite is generally spherical.

In example 17 the subject matter of the Examples 1-16 can optionallyinclude wherein in the first state the composite is generally planar.

An embodiment is represented in FIG. 5(a), which actuates more quicklythan other configurations. Some of the shapes are easier to crimp orform the “first state” of example 1 than others while still others mayactuate to the “second state” more readily than others.

Example 18 includes a hemorrhage management system comprising: a shapememory polymer (SMP) foam, including open cells, having first and secondstates; and a hydrogel (HG) included within the cells; wherein (a) in afirst position a composite, including the SMP foam and the HG, isconfigured to be located proximate a hemorrhagic tissue with the SMPfoam in the first state; (b) in a second position the composite isconfigured to be expanded to the second state against the hemorrhagictissue when the SMP foam is plasticized at 37° C. depressing a glasstransition temperature (T_(g)) of the SMP foam to below 25° C.

As used herein, a “hemorrhagic tissue” includes tissues that bleedslightly, profusely, and all points in between.

In example 19 the subject matter of Example 18 can optionally include asubstrate coupled to the composite, wherein the substrate includes amember selected from the group comprising gauze, bandage, and atourniquet.

For example, the coupling may be fixed (which can be “undone” withoutusing destructive force) or permanent (which cannot be “undone” withoutusing destructive force). The composite may extend in a rectangular“first state” along the underside of a gauze or adhesive bandage suchthat a user simply applies the bandage over a wound as one would do in aconventional manner and then allow the composite to actuate to thesecond state where the SMP foam expands and the HG swells.

In another version of example 19 the subject matter of Example 18 canoptionally include a substrate coupled to the composite, wherein thesubstrate includes a member selected from the group comprising gauze,bandage, hydrogel, skin substitute, and a tourniquet.

In example 20 the subject matter of the Examples 18-19 can optionallyinclude wherein (a) the SMP foam is crosslinked and includes struts,which form the cells, and the HG is crosslinked around struts; and (b)the SMP foam is a thermoset polymer that includes polyurethane.

The foregoing description of the embodiments of the invention has beenpresented for the purposes of illustration and description. It is notintended to be exhaustive or to limit the invention to the precise formsdisclosed. Persons skilled in the relevant art can appreciate that manymodifications and variations are possible in light of the aboveteaching. Persons skilled in the art will recognize various equivalentcombinations and substitutions for various components shown in theFigures. It is therefore intended that the scope of the invention belimited not by this detailed description, but rather by the claimsappended hereto.

Although the description above contains many details and specifics,these should not be construed as limiting the scope of the applicationbut as merely providing illustrations of some of the presently preferredembodiments of the apparatus, systems, and methods. Otherimplementations, enhancements and variations can be made based on whatis described and illustrated in this patent document. The features ofthe embodiments described herein may be combined in all possiblecombinations of methods, apparatus, modules, systems, and computerprogram products. Certain features that are described in this patentdocument in the context of separate embodiments can also be implementedin combination in a single embodiment. Conversely, various features thatare described in the context of a single embodiment can also beimplemented in multiple embodiments separately or in any suitablesubcombination. Moreover, although features may be described above asacting in certain combinations and even initially claimed as such, oneor more features from a claimed combination can in some cases be excisedfrom the combination, and the claimed combination may be directed to asubcombination or variation of a subcombination. Similarly, whileoperations are depicted in the drawings in a particular order, thisshould not be understood as requiring that such operations be performedin the particular order shown or in sequential order, or that allillustrated operations be performed, to achieve desirable results.Moreover, the separation of various system components in the embodimentsdescribed above should not be understood as requiring such separation inall embodiments.

Therefore, it will be appreciated that the scope of the presentapplication fully encompasses other embodiments which may become obviousto those skilled in the art. In the claims, reference to an element inthe singular is not intended to mean “one and only one” unlessexplicitly so stated, but rather “one or more.” All structural andfunctional equivalents to the elements of the above-described preferredembodiment that are known to those of ordinary skill in the art areexpressly incorporated herein by reference and are intended to beencompassed by the present claims. Moreover, it is not necessary for adevice to address each and every problem sought to be solved by thepresent apparatus, systems, and methods, for it to be encompassed by thepresent claims. Furthermore, no element or component in the presentdisclosure is intended to be dedicated to the public regardless ofwhether the element or component is explicitly recited in the claims. Noclaim element herein is to be construed under the provisions of 35U.S.C. 112, sixth paragraph, unless the element is expressly recitedusing the phrase “means for.”

While the apparatus, systems, and methods may be susceptible to variousmodifications and alternative forms, specific embodiments have beenshown by way of example in the drawings and have been described indetail herein. However, it should be understood that the application isnot intended to be limited to the particular forms disclosed. Rather,the application is to cover all modifications, equivalents, andalternatives falling within the spirit and scope of the application asdefined by the following appended claims.

The invention claimed is:
 1. A system comprising: a shape memory polymer(SMP) foam, including open cells, having first and second states; and ahydrogel (HG) included within the cells; wherein (a) in a first positiona composite, including the SMP foam and the HG, is configured to belocated in a wound with the SMP foam in the first state; (b) in a secondposition the composite is configured to expand to the second state inthe wound when the SMP foam is plasticized at 37° C. depressing a glasstransition temperature (Tg) of the SMP foam to below 25° C.
 2. Thesystem of claim 1, wherein the SMP foam includes polyurethane and the HGincludes Poly(ethylene glycol) Diacrylate (PEG-DA) N-vinylpyrrolidone(NVP) (PEG-DANVPHG).
 3. The system of claim 2, wherein the SMP foamincludes at least two of Hexamethylene diisocyanate (HDI),triethanolamine (TEA), hydroxypropyl ethylenediamine (HPED), orcombinations thereof.
 4. The system of claim 1, wherein the SMP foamactuates at body temperature.
 5. The system of claim 3, wherein the HGincludes an antimicrobial agent.
 6. The system of claim 5, wherein theantimicrobial agent includes iodine.
 7. The system of claim 1, wherein:the HG includes iodine and polyvinylpyrrolidone (PVP); and the iodine isbound to the PVP.
 8. The system of claim 1 comprising an applicator thatincludes the composite and a plurality of additional composites, each ofthe additional composites including an additional SMP foam withadditional cells that include additional HGs.
 9. The system of claim 1,wherein the SMP foam is configured to conform to contours of the wound,when in the second position and the second state, based on the SMP foamhaving a % Shape Recovery greater than 85, an expansion ratio greaterthan 4.00, and a swellability (Q) greater than 20 where Q=(mass ofsaturated device)/(mass of dry device).
 10. The system of claim 1,wherein: the SMP foam is crosslinked; the SMP foam includes struts; thestruts form the cells, and the HG is crosslinked around the struts. 11.The system of claim 1, wherein the SMP foam is a thermoset polymer thatincludes polyurethane.
 12. A medical implant system comprising: a shapememory polymer (SMP) foam having open cells; and a hydrogel (HG)included within the cells; wherein the SMP foam plasticizes at 37° C. todepress a glass transition temperature (Tg) of the SMP foam to below 25°C.; wherein the SMP foam is crosslinked and includes struts; wherein thestruts form the open cells; wherein the HG is crosslinked around thestruts.
 13. The medical implant system of claim 12, wherein the SMP foamis a thermoset polymer that includes polyurethane.
 14. The medicalimplant system of claim 13, wherein the SMP foam includes at least twoof Hexamethylene diisocyanate (HDI), triethanolamine (TEA),hydroxypropyl ethylenediamine (HPED), or combinations thereof.
 15. Themedical implant system of claim 14, wherein the HG includesPoly(ethylene glycol) Diacrylate (PEG-DA) N-vinylpyrrolidone (NVP)(PEG-DANVPHG).
 16. The medical implant system of claim 12, wherein: theSMP foam includes polyurethane; the HG includes iodine andpolyvinylpyrrolidone (PVP); and the iodine is bound to the PVP.
 17. Amethod comprising: providing a shape memory polymer (SMP) foam havingopen cells, wherein (a) the SMP foam is crosslinked and includes struts,and (b) the struts form portions of the open cells; inserting a hydrogel(HG) into the open cells; and heating the SMP foam and the HG tocrosslink the HG around the struts; wherein the SMP foam plasticizes at37° C. to depress a glass transition temperature (Tg) of the SMP foam tobelow 25° C.
 18. The method of claim 17, wherein the SMP foam is athermoset polymer that includes polyurethane.
 19. The method of claim18, wherein the HG includes Poly(ethylene glycol) Diacrylate (PEG-DA)N-vinylpyrrolidone (NVP) (PEG-DANVPHG).
 20. The method of claim 19,wherein the SMP foam includes at least two of Hexamethylene diisocyanate(HDI), triethanolamine (TEA), hydroxypropyl ethylenediamine (HPED), orcombinations thereof.